Imidazole → O-methyl-N-trityl-D-serine

HRID 534696Notes

Reaction equation

HRID 534696 reaction equation
N1C=CN=[CH:2]1.[H-].[Na+].[C:8]([NH:27][C@@H:28]([C:31]([OH:33])=[O:32])[CH2:29][OH:30])([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.CI>C(O)(=O)C.O.O1CCCC1>[CH3:2][O:30][CH2:29][C@H:28]([C:31]([OH:33])=[O:32])[NH:27][C:8]([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)([C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1)[C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=1

Participants

8

Reactant 4

HCID 795ImidazoleHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 12042811N-(Triphenylmethyl)-D-serine

Product 1

HCID 57734153O-methyl-N-trityl-D-serine

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To the stirred and cooled (at −15° C. to −10° C.) suspension of tetrahydrofuran (250 ml), imidazole (1.95 g) and sodium hydride (12.66 g), solid N-trityl-D-serine (50 g) was added in lots at an interval of 10 minutes. It was stirred for 45 minutes at −15° C. to −10° C. and then methyl iodide (40.85 g) was added to it at the same temperature (mild exothermic reaction was observed). The temperature of the reaction mass was raised to −5° C. to 0° C. and then it was stirred for 3 hours at the same temperature. De-ionized water (100 ml) was added to it and the reaction mass was cooled to 0° C. to 5° C. Acetic acid (9.8 ml) was added to the reaction mass and pH of the mass was adjusted to 6.5 to 7.0. Tetrahydrofuran was recovered completely under vacuum at 30° C. to 35° C. and dichloromethane (100 ml) and de-ionized water (100 ml) were added to the reaction mass at ambient temperature. This was stirred and allowed to settle for 15 minutes. The layers were separated. Dichloromethane (50 ml×2) was added to the aqueous layer, stirred, allowed to settle and layers were separated. The obtained organic layers were combined and de-ionized water (100 ml) was added to it. This was stirred, allowed to settle and then organic layer was separated. Anhydrous sodium sulphate (5 g) was added to the organic layer. It was stirred for 20 minutes and filtered through hyflo bed.

Workup

  1. temperaturecooled
  2. additionwas added in lots at an interval of 10 minutes
  3. stirringIt was stirred for 45 minutes at −15° C. to −10° C.
  4. temperatureThe temperature of the reaction mass was raised to −5° C. to 0° C.
  5. stirringit was stirred for 3 hours at the same temperature
  6. temperaturethe reaction mass was cooled to 0° C. to 5° C
  7. customTetrahydrofuran was recovered completely under vacuum at 30° C. to 35° C.
  8. additiondichloromethane (100 ml) and de-ionized water (100 ml) were added to the reaction mass at ambient temperature
  9. stirringThis was stirred
  10. customThe layers were separated
  11. additionDichloromethane (50 ml×2) was added to the aqueous layer
  12. stirringstirred
  13. customlayers were separated
  14. additionde-ionized water (100 ml) was added to it
  15. stirringThis was stirred
  16. customorganic layer was separated
  17. additionAnhydrous sodium sulphate (5 g) was added to the organic layer
  18. stirringIt was stirred for 20 minutes
  19. filtrationfiltered through hyflo bed

Sources & evidence

ORD record
ord-6f163fa226084e06901c78e3ffce3d7d
Source dataset
uspto-grants-2014_10
Patent number
US08853453B2

Reaction notes

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